{"title":"临床表现为进行性非流利性失语的非典型TDP-43蛋白病:病例报告。","authors":"Yuki Suzuki, Tadashi Adachi, Kentaro Yoshida, Kenta Taneda, Mayuko Sakuwa, Masato Hasegawa, Ritsuko Hanajima","doi":"10.1111/neup.12942","DOIUrl":null,"url":null,"abstract":"<p><p>Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.\",\"authors\":\"Yuki Suzuki, Tadashi Adachi, Kentaro Yoshida, Kenta Taneda, Mayuko Sakuwa, Masato Hasegawa, Ritsuko Hanajima\",\"doi\":\"10.1111/neup.12942\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.</p>\",\"PeriodicalId\":19204,\"journal\":{\"name\":\"Neuropathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/neup.12942\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/neup.12942","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/17 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
进行性非流利性失语症(PNFA)是额颞叶变性(FTLD)的一种形式,由 tau 和 43 kDa 的转录反应 DNA 结合蛋白(TDP-43)累积引起。在此,我们报告了一名 64 岁右撇子男子的尸检结果,他患有非典型 TDP-43 蛋白病,在死亡前的 36 个月里出现了语言障碍、言语瘫痪和吞咽困难。直到去世前,他都没有出现锥体束症状。尸检时,脑部宏观检查显示,左侧优势前额回、上额回和中额回萎缩,普坦门变色。前额叶、额上叶、额中叶回和颞叶尖端的皮质表面出现严重的海绵样变和神经元缺失。抗磷酸化TDP-43免疫染色显示,额叶皮质中存在神经元胞浆包涵体和长而短的萎缩性神经元。对沙可糖不溶性部分的免疫印迹分析显示,TDP-43的过度磷酸化条带为45 kDa,磷酸化的C端片段约为25 kDa。病理分布和免疫印迹条带模式与主要的TDP-43亚型不同,因此可能代表了一种新的FTLD-TDP表型。
Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.
Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.
期刊介绍:
Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.